Continued computer‐assisted structural design led to a tripeptide containing benzothiazole as a warhead group and an m‐N,N‐dimethylaminophenyl group as P4‐moiety (71). 160  This compound was extremely potent in inhibiting Mpro of SARS‐CoV‐1 with a K i value of 3.1 nM. Docking studies of 71 confirmed that the benzothiazole group was tightly bound to the active site. Consequently, the same research group disclosed a series of dipeptides with reduced molecular weight in an attempt to improve drug‐like properties. The P3‐valine in the tripeptide 71 was exchanged for a variety of functional groups. 161  The study determined N‐arylglycyl to be the optimal P3‐moiety. Compound 72 displayed the best inhibitory activity. Docking studies of 72 to the protease highlighted the amino hydrogen of the P3‐N‐phenyl glycyl forming a H‐bond with backbone Glu166 of Mpro, in addition to the best P2‐leucine and P1'‐benzthiazole moieties (see Figure 23A). Further structural optimization at the P3‐N‐arylglycyl moiety found the indole‐2 carbonyl group to be one of the best P3‐moeities, thus reaching inhibitors with low nanomolar potency, for example 73 (K i, 0.006 µM) against SARS‐CoV‐1 Mpro. 162  Docking studies of compound 73 to the protease revealed that the indole amino hydrogen and the carbonyl group attached to the 2‐position formed H‐bond interactions with the backbone Glu166 (see Figure 23B). These interactions are of great importance, seeing as shifting the position of the carbonyl group from position 2 to 3, or replacing the indole with benzofuran drastically reduced inhibitory potency.